Thanks to DNA sequencing, patients with rare cancers for
which no standard treatment is available could receive existing
therapies that work in patients treated for different cancers, but
who carry the same genetic mutations. The first results of a
multi-drug and multi-tumour clinical trial, presented at the ESMO
2017 Congress, show that this kind of precision oncology trial is
not only feasible, but also has the potential to identify patient
subgroups who could benefit from existing drugs outside of their
In the Netherlands, a network of more than 40 hospitals
systematically performs Whole Genome Sequencing (WGS) on patients
with metastatic cancer in order to create a database that now
comprises about 2,000 individuals treated for all types of
"By sequencing the whole genome in so many patients, we found
commonalities between tumours and DNA mistakes. For example, the
ERBB2 gene is mainly screened for in breast cancer patients, but we
know that it is also present in patients with other tumour types,"
said principal study investigator Prof. Emile Voest, from the
Netherlands Cancer Institute in Amsterdam.
"Now that we are able to identify these patients, the question
is: How can we get them to benefit from existing, potentially
active drugs? That is the basis for our Drug Rediscovery Protocol,
which currently includes 19 different drugs from 10 pharmaceutical
companies," Voest reported.
Since the trial was launched in late 2016, over 250 cases have
been submitted for review: Of these, about 70 patients have so far
been found eligible and started treatment. Adult patients with
solid tumours, glioblastoma, lymphoma or multiple myeloma with no
standard treatment options were enrolled in the study in multiple
parallel cohorts according to tumour type and trial drug.
"We have preclinical evidence and case reports suggesting
that certain drugs, which patients with a given genetic aberration
and a certain type of cancer are sensitive to, could equally be
active in patients with the same mutation in other tumour groups.
However, we also know that the tissue background is extremely
important: That's why we create study cohorts not just according
The efficacy of the treatment for each cohort is analysed in a
two-stage process: "If in stage one, the first group of eight
patients with the same tumour type and genetic mutation responds to
the treatment, we expand the cohort to 24 patients in stage two to
get a stronger indication of the clinical benefit," said Voest.
"Clinical benefit, in this case, is defined as either a complete
remission, a partial response, where the tumour shrinks by more
than 50 percent, or disease stability for at least 16
To date, a clinical benefit has been observed in 37 percent of
trial participants, and six of the 20 study cohorts have graduated
to stage two. "We've seen real success with several anticancer
drugs, including immunotherapy, a PARP inhibitor and an antibody
combination," Voest reported.
"Our team is quite excited about these results, because
everybody knows that developing new drugs is very expensive. With
this study, we are providing a platform for expanding the
indications of existing drugs and utilising them to their full
potential," he said. "Using drugs that are already available based
on DNA sequencing is a truly novel approach to personalising
medicine, and we are talking to regulatory authorities to see how
new findings in this area can be translated to the clinic as
quickly as possible for these rare subsets of patients."